Evidence that fibrates have clinical benefits is mixed.
Fibrates primarily reduce levels of triglycerides with only modest effects on low density and high density lipoprotein cholesterol.
Fibrates modulate bile-acid homeostasis through activation of the peroxisome proliferator-activated receptor (PPAR).
Fibric acid derivatives, or fibrates, are agonists of the peroxisome proliferator activator receptor (PPAR), a nuclear receptor involved in several metabolic pathways.
In the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) showed that fenofibrate plus statins in patients with type 2 diabetes did not reduce cardiovascular events more than the use of statins alone.
Gemfibrozil and fenofibrate are available in the US.
Fibrates lower TG levels but do not significantly lower coronary heart disease events and actually can increase serious adverse effects when combined with statins.
A class of amphipathic carboxylic acids, used for a range of metabolic disorders, mainly hypercholesterolemia.
Used in accessory therapy in many forms of hypercholesterolemia, usually in combination with statins.
Clinical trials do support their use as monotherapy agents.
Fibrates reduce the number of non-fatal heart attacks, but do not improve all-cause mortality and are therefore indicated only in those not tolerant to statins.
Although less effective in lowering LDL levels, the ability of fibrates to increase HDL and lower triglyceride levels seems to reduce insulin resistance when the dyslipidemia is associated with other features of the metabolic syndrome.
Rarely and paradoxically may decrease HDL-C in some patients, it is recommended that the HDL-C levels be checked within the first few months after initiation of fibrate therapy.
Most fibrates can cause mild stomach upset and myopathy.
They increase the cholesterol content of bile, they increase the risk for gallstones.
In combination with statin drugs, fibrates cause an increased risk of rhabdomyolysis.
Drug toxicity includes acute kidney injury.
They activate PPAR (peroxisome proliferator-activated receptors).
The PPARs are a class of intracellular receptors that modulate carbohydrate and fat metabolism and adipose tissue differentiation.
Activating PPARs induces the transcription of a number of genes that facilitate lipid metabolism.
Fibrates are structurally and pharmacologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs.
Fibrates are metabolized by CYP3A4.
Fibrates improve liver biochemistries in patients with primary biliary cholangitis who are treatment-naïve or who lack complete response to UDCA.
In the PROMINENT trial using Pemafibrate in a randomized trial of diabetics: it lower triglyceride levels by 26% and increased HDL cholesterol levels by 5%, but did not reduce the incidence of events of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes.
In this study pemafibrate had a higher incidence of renal events and venous thromboembolism, but a lower level of nonalcoholic fatty liver disease.